DESCRIPTION: This is a revised version of an application originally submitted in response to RFA #HL-96-018. The proposal is aimed at testing the hypothesis that homocysteinemia contributes to the development of atherosclerosis primarily by altering the cellular functions of inflammatory cells. The application consists of two Specific Aims. Under the first, the investigator will determine whether plasma homocysteine (HC) stimulates an increased fibroproliferative response in vivo in hypercholesterolemic mice with homocysteinemia. Under Aim 2, the investigator will determine the mechanism by which HC and lipid accumulation alter glutathione and NADH/NADPH metabolism, thereby activating macrophages in vitro.